Alkyl esters, cross-coupling

Oxidative cross-coupling reactions of alkylated derivatives of activated CH compounds, such as malonic esters, acetylacetone, cyanoacetates, and certain ketones, with nitroalkanes promoted by silver nitrate or iodine lead to the formation of the nitroalkylated products.67 This is an alternative way of performing SRN1 reactions using a-halo-nitroalkanes. 

This route involves the conversion of a 3,4-diiodopyrrole (139) to the corresponding 3,4-diboronate ester (140) followed by a bis Suzuki cross-coupling reaction with a bromoquinoline, which generates the halitulin core (141). This pyrrole (141) is then alkylated with a tosylated cycloazadecane to generate a pentasubstituted pyrrole (143), which is converted to halitulin by debenzylation under hydrogenolysis conditions. 

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

A prototypical study for this section has been obtained as early as in 1983 for carbonylative cross-coupling of the mixture of aryl iodide and alkyl iodide in the presence of Zn metal and palladium catalyst. This system apparently works due to differences of reactivity of aryl versus alkyl iodide toward metallation by Zn. Further studies were rather scarce to involve only preformed functionalized alkylzincs. Carbonylative cross-coupling of functionalized organozinc reagents with allylic esters and GO (1 atm) can be carried out in THF in the presence of HMPA, which suppresses side-reactions (Scheme 4). ... 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

Savarin, C. Srogl, J. Liebeskind, L. S. Thiol ester-boronic acid cross-coupling. Catalysis using alkylative activation of the Pd thiolate intermediate. Org. Lett. 2000, 2, 3229-3231. 

The peroxidase-catalyzed oxidation of 2,2 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), o-phenylene-diamine (PDA), and 3,3, 5,5 -tetramethylbenzidine (TMB) was found to be activated by tetrazole 2 and 5-aminote-trazole and weakly inhibited by 1,5-diaminotetrazole 33 <2004MI283>. Bhattacharya and Vemula studied the effect of heteroatom insertion in the side chain of 5-alkyl-177-tetrazoles on their properties as catalysts for ester hydrolysis at neutral pH <2005JOC9677>. l-(2-Iodophenyl)-177-tetrazole was successfully used in Heck reactions to give the cross-coupled products in excellent yield <2004TL4113>. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

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